ISSN  2587-2362  |  E-ISSN  2618-642X
International Journal of Medical Biochemistry - Int J Med Biochem : 5 (1)
Volume: 5  Issue: 1 - 2022
1.Does dietary restriction of amino acids other than methionine have any effect on peroxide and superoxide production rates, oxidative protein and DNA damage in the liver and heart mitochondria of aging rats?
Sevda Tanrıkulu Küçük, Evin Ademoğlu
doi: 10.14744/ijmb.2021.29981  Pages 1 - 7
INTRODUCTION: The objective of this study was to evaluate the long-term effects of amino acids other than methionine in mitotic and postmitotic tissue of rats by measuring mitochondrial peroxide and superoxide production as well as oxidative protein and DNA damage in the liver and heart of rats fed with either a normal diet (ND) or a protein-restricted diet (PREMD).
METHODS: The study group comprised 4- and 12-month-old rats fed with either a ND or a PREMD for 4 months. The rate of mitochondrial peroxide and superoxide production, and the protein carbonyl (PC) and mitochondrial DNA (mtDNA) 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the liver and heart mitochondria were measured.
RESULTS: The mitochondrial peroxide and superoxide production rates of the liver and heart mitochondria of rats did not demonstrate any significant difference based on the diet provided. Similarly, diet did not have a significant effect on the PC level in the liver and heart mitochondria of either age group. In the 16-month-old rats, the mtDNA 8-OHdG level was significantly higher in the heart than the liver, regardless of the diet.
DISCUSSION AND CONCLUSION: Mitochondrial reactive oxygen species production, and oxidative protein and DNA damage increased in mitotic and postmitotic tissue with age; however, the increment was more prominent in the heart than the liver. Longterm PREMD consumption did not decelerate oxidative damage in the heart or in the liver with age.

2.Evaluation of the relationship between C-Reactive Protein/Albumin Ratio and Hospitalization in Novel Coronavirus disease-19 (COVID-19)
Çiğdem Damla Deniz, Nahide Baran, Ayse Rüveyda Ugur, Ahmet Güneyk, Mehmet Özcan, İsmail Hakkı Tunçez, Mehmet Koç
doi: 10.14744/ijmb.2021.57070  Pages 8 - 14
INTRODUCTION: Coronavirus disease 2019 (COVID-19), a global pandemic with catastrophic consequences for healthcare systems causing serious respiratory illness, was first reported in China. Early identification of severe illness is critical for controlling it and improving the prognosis of patients. In this study, we aimed to evaluate the prognostic value of Creactive protein (CRP)/albumin ratio and to investigate the usability of this ratio in COVID-19.
METHODS: This was a retrospective cohort study of 1077 patients. The statistical significance was calculated using Mann-Whitney U test. The correlations between CRP/albumin ratio and other datas were evaluated by Spearman’s rho test. We evaluated the prognostic value of CRP/albumin ratio using the Chi-Square test and Cox regression analysis.
RESULTS: Higher CRP/albumin ratio levels were associated with long-term hospitalization in COVID-19. When the results of the receiver operating characteristic analysis were examined for all laboratory parameters, the area under the curve value of the CRP/albumin ratio, procalcitonin, CRP, and albumin were 0.85, 0.64, 0.86, and 0.81, respectively. The survival mortality cut-off value for CRP/albumin ratio was determined as 1.895. When evaluated by Cox regression analysis (cutoff value: 1.895, p<0.0001), the CRP/albumin ratio was found to be independently associated with in-hospital mortality.
DISCUSSION AND CONCLUSION: We showed that the CRP/albumin ratio is a useful prognostic marker this marker can be used in predicting the severity of COVID-19.

3.Correlation of neutrophil-lymphocyte ratio, plateletlymphocyte ratio and mean platelet volume with disease activity in patients with ankylosing spondylitis
Pulin Kumar Gupta, Ankita Sheoran, Manita Khatak, Kartik Balankhe, Saikiran Koner, Rishabh Nayak, Keshu Jindal, Saurabh Kumar Singh, Shrey Bhatt
doi: 10.14744/ijmb.2021.15013  Pages 15 - 20
INTRODUCTION: The indices that are currently used to determine the disease activity in patients with ankylosing spondylitis (AS) are either patient- or physician-oriented. The neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR) and mean platelet volume (MPV) are new markers of systemic inflammation and correlate with disease severity in many rheumatological disorders. However, their relationship with disease activity in patients with AS has not been thoroughly studied in the Indian subcontinent.
METHODS: This cross-sectional observational study was performed on 60 patients with definite AS in a tertiary care hospital in New Delhi, India. Healthy, age- and sex-matched individuals identified from the same demographic population were subjected to clinical assessment and investigations as per protocol.
RESULTS: The mean values of NLR, PLR and MPV were 3.13±1.1, 168.36±69.43 and 10.07±1.28, respectively, in cases with high disease activity as compared to 2.58±1.05, 127.02±55.65 and 10.07±1.64 in cases with low disease activity. A statistically significant correlation was found between NLR and PLR and disease activity as calculated by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Metrology Index (BASMI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Ankylosing Spondylitis Disease Activity Score-C-reactive protein/erythrocyte sedimentation rate (ASDAS-CRP/ESR). However, multivariate linear regression revealed a significant correlation only between NLR and BASDAI, BASFI and ASDAS-CRP. PLR was found to be significantly lower in cases on biological therapy. No correlation of PLR and MPV with disease activity was found on multivariate regression analysis.
DISCUSSION AND CONCLUSION: NLR and PLR correlate significantly with disease activity indices in patients with AS. Patients with the extraspinal disease had higher NLR, PLR and MPV with only NLR being statistically significant. NLR was significantly lower in patients on biologics than those on Disease modifying antirheumatic drugs (DMARDs). Therefore, NLR and PLR can be used as potential parameters for the assessment of disease activity and extra-spinal disease and treatment response monitoring in patients with AS.

4.Importance of detecting hyperlipidemia in children and adolescents to manage cardiovascular risk: A cross-sectional study
Hacer Eroğlu, Arif Murat Kaytaz, Evin Ademoglu, Sema Genc
doi: 10.14744/ijmb.2021.28190  Pages 21 - 27
INTRODUCTION: As childhood and adolescence are the periods when cardiovascular risk factors begin to emerge, this study aimed to investigate the serum lipid profiles of the pediatric population in age- and sex-specific partitions.
METHODS: The serum lipids were measured in 9613 pediatric samples from residual material in the Istanbul Public Health Laboratory with age groups stratified as 1-4 years, 5-9 years, 10-14 years, and 15-19 years.
RESULTS: The total-C and LDL-C were significantly high in girls aged 1-4 years, and total-C and LDL-C were significantly low in boys aged 15-19 years. Total-C levels of girls were also different at ages 1-4 and 15-19 years compared with boys. The girls also showed higher LDL-C levels at 1-4 and 15-19 years, non-HDL-C levels at 1-4 years, 5-9 years, and 15-19 years, and HDL-C at 15-19 years compared with the boys of the same age group. The prevalence of hypertriglyceridemia, hypercholesterolemia, and high LDL-C in the 15-19 age groups was significantly different between boys and girls.
DISCUSSION AND CONCLUSION: This study emphasizes the importance of determining lipid profiles during childhood and adolescence and taking preventive actions for cardiovascular diseases by implementing reliable age- and sex-specific cut-off values.

5.Ischemia modified albumin level and thiol/disulfide homeostasis in the etiology of tinnitus
Hüseyin Kurku, Mehmet Akif Bor, Mustafa Faris Tulgar, Salim Neselioglu, Necat Alatas
doi: 10.14744/ijmb.2021.92485  Pages 28 - 33
INTRODUCTION: Although many theories about the etiology of tinnitus have been proposed, it has not been fully clarified. In this study, we investigated the role of ischemia in the etiology of tinnitus.
METHODS: A total of 90 participants, 50 tinnitus patients and 40 controls, were included in this study. Total thiol (TT), native thiol (NT), NT/TT ratio, disulfide, disulfide/TT ratio, disulfide/NT ratio, ischemia-modified albumin (IMA), and IMA/albumin ratio (IMA/AlbR) values of tinnitus patient group and controls were compared and receiver operating characteristic (ROC) analyses conducted.
RESULTS: IMA (0.767±0.06) and IMA/AlbR (17.71±2.46) values were statistically significantly higher in the tinnitus group than in the control group (0.742±0.06 vs. 16.00±2.48 and p=0.040 vs. p=0.002, Independent Samples test). No statistically significant difference was observed between the groups for the other parameters. While albumin was presenting a perfect positive correlation with TT and NT, IMA showed rugged negative parallelism with NT and TT, similar to that of IMA/AlbR. According to ROC analysis, a cut-off value of 14.29 was found to be statistically significant for IMA/AlbR in distinguishing patients with tinnitus from the controls (sensitivity of 96%, specificity of 32.5%, AUC: 0.676, and p=0.002).
DISCUSSION AND CONCLUSION: In the present study, in the tinnitus group, higher values of IMA and IMA/AlbR, which are markers of ischemic status, support the theory specifying that ischemia has an influential role in the etiology of tinnitus.

6.Comparison of inflammation markers in different severities of COVID-19 disease
Muzaffer Katar, Yalçın Önder, Rıza Citil, Osman Demir, Tuncay Yigit
doi: 10.14744/ijmb.2021.39358  Pages 34 - 43
INTRODUCTION: We retrospectively analyzed COVID-19 patients for clinical and hematologic features and tried to define the most appropriate markers to diagnose and predict the severity.
METHODS: This is a retrospective cross-sectional study. All 4443 patients included were diagnosed with reverse trancription-polymerase chain reaction between January 1 and December 30, 2020. We classified patients according to their mode of treatment: outpatient, inpatient in the ward, or inpatients in the intensive care unit (ICU).
RESULTS: The mean age of 2283 (51.4%) women and 2160 (48.6%) men included in the study was determined to be 39.77±17.30. Of the 4443 patients, 3985 (89.7%) were outpatients, 330 (7.4%) were inpatients, and 128 (2.9%) patients were treated in the ICU. The mean hospital stay was 8.36±4.55 days for the survivors in the ward group and 2.67±1.53 days for those who died (p=0.031). The mean hospitalization time of the survivors in the ICU group was 19.97±12.09 days, and the mean hospitalization time of the deceased was 13.10±9.99 days (p=0.001). Age, ferritin, D-dimer, glucose, ALT, AST, urea, creatinine, CRP, HgA1c, IMG, IMG%, and RDW-SD showed a gradual and significant increase in outpatient, ward, and ICU groups (p<0.001). Na, K, Neu, Neu%, MCV, RDW-CV, MPV, NLR, PLR, and NMR increased gradually from the outpatient group to the service and ICU groups, whereas Ca, RBC, Hgb, and Hct values decreased significantly (p<0.001). WBC, lymph%, and RDW were highest in the ICU group.
DISCUSSION AND CONCLUSION: Advanced age and being male are important risk factors for hospitalization. Indexes such as NLR, PLR, LCR, NMR, and LMR can be used to predict the severity of the disease.

7.Estimated glomerular filtration rate in identifying illness severity in newly admitted patients with COVID-19: A single-center study
Yasemin Ustundag, Fatma Tuba Engindeniz, Kağan Huysal, Rahime Feyza Koloğlu, Ali Asan, Nizameddin Koca, Cuma Bulent Gul, Canan Erdem, Cuneyt Eris, Emine Sevgican
doi: 10.14744/ijmb.2021.60783  Pages 44 - 48
INTRODUCTION: Early prediction of risk factors for serious illness and death in patients with coronavirus disease 2019 (COVID-19) appears to be a priority. This study aimed to examine whether a single estimated glomerular filtration rate (eGFR) at triage predicts the need for intensive care unit (ICU) admission of patients with COVID-19.
METHODS: This retrospective study included data from patients with COVID-19 at the Bursa Yuksek Ihtisas Training and Research Hospital until October 2020. Patients were assigned to two groups according to their eGFR level at admission: group 1 (eGFR >60 mL/min/1.73 m2) and group 2 (eGFR=30-60 mL/min/1.73 m2).
RESULTS: The results of 1447 consecutive patients diagnosed with COVID-19 were analyzed at hospital admissions. Of these, 1001 patients who met the study criteria were included in the study. The median age of group 2 was higher than group 1: 69 interquartile range (IQR 23) years versus 39 (IQR 23) years (p<0.01). Patients with an eGFR <60 mL/min/1.73 m2 had lower lymphocyte counts while having higher C-reactive protein, d-dimer, lactate dehydrogenase, and fibrinogen levels. The ICU admissions were significantly higher in patients with a baseline eGFR <60 mL/min/1.73 m2 (42.85%) compared with an eGFR >60 mL/min/1.73 m2 (6.42%, p<0.001). There was a weak negative correlation between eGFR and ICU admission (rho=-0.291, p<0.001).
DISCUSSION AND CONCLUSION: The eGFR at admission was strongly correlated with the severity of the disease. Therefore, measuring eGFR in all patients at admission may warrant appropriate triage.

8.Evaluation of babies with hyperphenylalaninemia diagnosed in the National Newborn Screening Program in Istanbul in 2019
Pelin Savli, Melike Ersoy, Abdullah Emre Güner, Ibrahim Taş
doi: 10.14744/ijmb.2021.44127  Pages 49 - 53
INTRODUCTION: To evaluate the 2-year follow-up of hyperphenylalaninemia (HPA) patients born in 2019.
METHODS: Growth, neuromotor development, and vitamin levels of 61 two-year-old babies followed up with the diagnosis of HPA in 2019 were evaluated.
RESULTS: Thirty-six (59.02%) of the cases were female. The mean birth weight of the babies was 3198.7±504 g and 23.1% (n=14) of them were preterm. The mean of initial National Newborn Screening Program phenylalanine (phe) levels was 3.85±1.86 mg/dL. The mean day to diagnosis was 13.29 days (range 4-18). Forty-eight (78.7%) of the patients declared sufficient knowledge about HPA follow-up. Follow-up compliance of the families was 67%. Among the infants who participated in our study, 4 (6.6%) patients were diagnosed with sapropterin dihydrochloride (BH4) responsive mild phenylketonuria (MPKU). No patient was started on with phe-restricted diet therapy. The remaining 32 (52.4%) infants were followed up with the diagnosis of female HPA. The follow-up of 25 (41%) male infants was terminated. Anemia was found in 4 (6.6%) babies. Iron deficiency in 4 (6.6%) and B12 deficiency in 9 (14.8%) babies were detected. There was no significant difference between MPKU and HPA groups regarding growth parameters and vitamin levels.
DISCUSSION AND CONCLUSION: No growth or neuromotor retardation was found in HPA patients. Vitamin D and, less frequently, vitamin B12 deficiencies are prominent. No difference was observed between the patients who passed from HPA to MPKU and HPA cases, in terms of growth, development, and nutritional status.

9.Evaluation of total antioxidant capacity in human seminal plasma
Meltem Demir, Sebahat Ozdem
doi: 10.14744/ijmb.2021.30092  Pages 54 - 59
INTRODUCTION: Male factor infertility accounts for up to half of all cases of infertility. Oxidative stress (OS) is a condition associated with an increased rate of cellular damage induced by oxygen and oxygen-derived oxidants, commonly known as reactive oxygen species (ROS).
METHODS: Semen samples were obtained from 65 males aged 23-36 years who were a partner in an infertile couple and presented at the urology clinic of Antalya Medicalpark hospital. Routine spermiogram parameters were analyzed according to World Health Organization guidelines. The study was conducted using a normozoospermic group (n=18) with normal semen parameters, and 47 men with abnormal semen parameters; azoospermic (n=16), teratozoospermic (n=16) and oligoasthenoteratozoospermic (n=15). The total oxidant status (TOS), total antioxidant capacity (TAC), activity, and advanced oxidation protein products (AOPPs) levels in semen were determined using spectrophotometric method. The oxidative stress index (OSI) value of the seminal plasma was calculated. The results were analyzed statistically.
RESULTS: The AOPPs level, TOS activity and OSI index value in seminal plasma was significantly higher in the oligoasthenozoospermic, teratozoospermic and azospermic groups compared with the normozoospermic group. In contrast, the TAC activity was higher in normozoospermic group than infertile group.
DISCUSSION AND CONCLUSION: This study investigated whether the antioxidant status and the extent of protein oxidation in seminal plasma could be a valuable predictor of sperm function. The results suggest that TAC assay and OSI index may be useful markers for male infertility.

10.Total analytical error assessment of Yerköy State Hospital biochemistry laboratory
Meltem Yardım
doi: 10.14744/ijmb.2021.73745  Pages 60 - 66
INTRODUCTION: In 2016, the maximum allowable CV% and allowable total error limits (TEa-TR) for 15 test parameters were specified by the Ministry of Health of Turkey and put into practice. Our study aimed to assess the analytical performance of 15 test parameters studied in our laboratory in terms of the TEa-TR criteria and demonstrate the effect of the method of CV% use in the TAE formula on the performance of tests when two-level internal quality control (IQC) was employed.
METHODS: Total analytical error (TAE) was calculated using the formula TAE%=(CV%×1.65)+bias%. Two different procedures were followed for TAE calculation. TAE1 and TAE2 were separately calculated for each control level using the CV% values obtained from the data of IQC at two different levels used for each test. In addition, TAE3 values were found for each test parameter in line with the total CV% value (Total CV%=√(CV12+CV22) obtained using the IQC data from two different levels.
RESULTS: When CV% values were separately taken for each control level, the maximum allowable CV% value was exceeded in two tests at IQC Level 2, whereas the TEa-TR limit was exceeded in two tests at IQC Level 1 and in 2 tests at IQC Level 2 during the 6-month period. According to the TEa-TR formula, the allowable CV% was exceeded 19 times in 13 out of 15 tests, and TEa limits were exceeded 15 times in 10 tests during the 6-month period
DISCUSSION AND CONCLUSION: When the total CV% was calculated from Level 1 and Level 2 according to the TEa-TR formula, both the maximum allowable CV% and allowable TEa% limits were exceeded many times. However, when the CV% and TAE values were calculated separately for different levels of IQC samples, the analytical performance of the tests were found better. We think that calculating the TAE and CV% values separately is more useful in showing the analytical performance of the test at different levels.

11.Estimation of measurement uncertainty of glycated hemoglobin at Atellica Solutions
Funda Eren, Esra Fırat Oğuz
doi: 10.14744/ijmb.2021.84755  Pages 67 - 70
INTRODUCTION: Glycated hemoglobin (HbA1c) is a commonly used laboratory test for screening, monitoring, and diagnosing diabetes mellitus (DM). Uncertainty is a statistical expression that shows the effects of factors arising during measurement processes and affecting the reported results. It is important to give reliable laboratory results. This study aims to estimate the measurement uncertainty (MU) of HbA1c at Siemens Atellica Solutions.
METHODS: Internal and external quality control results of 6 months data were used to calculate the MU according to the Clinical & Laboratory Standards Institute (CLSI) document EP29-A. The coefficient of variation (CV%) of the two levels of internal quality control materials was calculated. The external quality control results of 6 months data obtained from the EQAS program of Bio-Rad were used to calculate the bias.
RESULTS: The precision results of the assay were within the current National Glycohemoglobin Standardization Program requirement of ≤4%. The HbA1c level above 6.5% is one of the diagnostic criteria of DM. We estimated the expanded uncertainty as 6.40% for HbA1c at the level of 6.5%. It is presented as 6.5±0.4%.
DISCUSSION AND CONCLUSION: It is important that laboratorians report accurate and reliable test results as clinicians make their decisions based on laboratory data. Laboratories should add measurement uncertainty results as a part of quality control programs. The laboratory tests with clinical decision limits should be presented with measurement uncertainty results.

12.Tools for evaluating the performance of HbA1c analyzer: Sigma Metric and Quality Goal Index Ratio
Yasemin Erdoğan Döventaş, Hatice Erdoğan
doi: 10.14744/ijmb.2021.77598  Pages 71 - 75
INTRODUCTION: Sigma metric model is one of the most popular quality management system tools used for Six Sigma process improvement. This model provides three features that improve the results: low inaccuracy, less deviation, and correct performance of the analytical method. Internal quality control and external quality assessment programs are routinely carried out in all clinical laboratories to evaluate and continually improve the analytical quality. The Six Sigma model is a global quality management system that can also be applied in the determination of glycated hemoglobin (HbA1c). In recent years, this model has been supported by Quality Goal Index (QGI). In this study, we aimed to evaluate the analytical performances of Arkray HA8180V HbA1c analyzer according to internal and external quality Sigma metrics and QGI.
METHODS: The data have been evaluated according to two internal control materials (Bio-DPC and KBUDEK External Quality Program) to calculate Sigma levels [Sigma=(TEa%-bias%)/CV%] and quality target indexes (QGI=bias/1.5×CV), where TEa is the total analytical error and CV is the coefficient of variation. QGI is a metric that can distinguish between techniques to deal with sensitivity and accuracy issues as well as calibrator lot changes.
RESULTS: The mean Sigma levels for low and high quality control materials were found to be 5.17 and 2.51, respectively. QGI was found to be 0.8 1.2 for both levels.

DISCUSSION AND CONCLUSION: The performance of HA8180V HbA1c analyzers was found to be acceptable compared to Sigma metrics. The values of OGI between 0.8 and 1.2 indicate inaccurate and inconsistent result. However, when evaluated as a whole with Sigma values, the results of the devices were found reliable.

13.Reviewer List 2021

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